At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral loa...At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral load,genotype,and specific viral mutations,are known to affect disease progression.HBV reverse transcriptase does not have a proofreading function,therefore,many HBV genotypes,sub-genotypes,mutants,and recombinants emerge.Differences between genotypes in response to antiviral treatment have been determined.To date,10 HBV genotypes,scattered across different geographical regions,have been identified.For example,genotype A has a tendency for chronicity,whereas viral mutations are frequently encountered in genotype C.Both chronicity and mutation frequency are common in genotype D.LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes.Pathogenic differences between HBV genotypes explain disease intensity,progression to LC,and HCC.In conclusion,genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.展开更多
BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the inf...BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.展开更多
Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascul...Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.展开更多
INTRODUCTIONMolecular biology has made a tremendous impact on thediagnosis and treatment of liver diseases.In particular,advances in molecular biology made possible the
Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)a...Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.展开更多
Exploration of natural sources for novel bioactive compounds has been an emerging field of medicine over the past decades,providing drugs or lead compounds of considerable therapeutic potential.This research has provi...Exploration of natural sources for novel bioactive compounds has been an emerging field of medicine over the past decades,providing drugs or lead compounds of considerable therapeutic potential.This research has provided exciting evidence on the isolation of microbe-derived metabolites having prospective biological activities.Mushrooms have been valued as traditional sources of natural bioactive compounds for many centuries and have been targeted as promising therapeutic agents.Many novel biologically active compounds have been reported as a result of research on medicinal mushrooms.In this review,we compile the information on bioactive structure-elucidated metabolites from macrofungi discovered over the last decade and highlight their unique chemical diversity and potential benefits to novel drug discovery.The main emphasis is on their anti-Alzheimer,antidiabetic,anti-malarial,anti-microbial,anti-oxidant,antitumor,anti-viral and hypocholesterolemic activities which are important medicinal targets in terms of drug discovery today.Moreover,the reader’s attention is brought to focus on mushroom products and food supplements available in the market with claimed biological activities and potential human health benefits.展开更多
A novel coronavirus known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread across the world,prompting the World Health Organization to declare the coronavirus disease of 2019(COVID-19)a public ...A novel coronavirus known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread across the world,prompting the World Health Organization to declare the coronavirus disease of 2019(COVID-19)a public health emergency of international concern.Cancer patients are regarded as a highly vulnerable population to SARS-CoV-2 infection and development of more severe COVID-19 symptoms,which is possibly due to the systemic immunosuppressive state caused directly by tumor growth and indirectly by effects of anticancer treatment.Currently,much effort has been directed toward studying the pathogenesis and treatment of COVID-19,but the risk profiles,prognoses,and treatment outcomes in cancer patients remain unclear.Based on the current literature,we summarize the risk profiles,clinical and biochemical characteristics,and therapy outcomes of COVID-19 infections in cancer patients.The challenges in the clinical care of cancer patients with COVID-19 are discussed.The goal of this review is to stimulate research to better understand the biological impact and prognoses of COVID-19 infections in cancer patients,thus facilitating improvement of the clinical management of these patients.展开更多
New hepatitis B virus(HBV)infections are decreasing owing to improved antiviral therapy and increased HBV vaccination worldwide;however,the number of HBV infections remains a major cause of liver carcinogenesis.HBV tr...New hepatitis B virus(HBV)infections are decreasing owing to improved antiviral therapy and increased HBV vaccination worldwide;however,the number of HBV infections remains a major cause of liver carcinogenesis.HBV triggers cytotoxic immunity to eliminate HBV-infected cells.Therefore,the HBV pathophysiology changes in persistently infected individuals depending on host immune responses and HBV DNA proliferation state.To prevent liver cirrhosis and carcinogenesis caused by HBV,it is important to treat HBV infection at an early stage.Active treatment is recommended for the immunoactive hepatitis B surface-antigen-positive and-negative phase,but not during the immune-inactive phase or immune-tolerant phase;instead,follow-up is recommended.However,these patients should be monitored through regular blood tests to accurately diagnose the immune-inactive or-tolerant phases.The treatment regimen should be determined based on the age,sex,family history of liver cancer,and liver fibrosis status of patients.Early treatment is often recommended due to various problems during the immune-tolerant phase.This review compares the four major international practice guidelines,including those from the Japanese Society of Hepatology,and discusses strategies for chronic hepatitis B treatment during the immune-tolerant,immune-inactive,and resolved phases.Finally,recommended hepatitis B antiviral therapy and follow-up protocols are discussed.展开更多
文摘At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral load,genotype,and specific viral mutations,are known to affect disease progression.HBV reverse transcriptase does not have a proofreading function,therefore,many HBV genotypes,sub-genotypes,mutants,and recombinants emerge.Differences between genotypes in response to antiviral treatment have been determined.To date,10 HBV genotypes,scattered across different geographical regions,have been identified.For example,genotype A has a tendency for chronicity,whereas viral mutations are frequently encountered in genotype C.Both chronicity and mutation frequency are common in genotype D.LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes.Pathogenic differences between HBV genotypes explain disease intensity,progression to LC,and HCC.In conclusion,genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.
基金This study was supported by a grant from the Scientific and Technology Bureau of Hubei Province Foundation(No.2005AA301C26).
文摘BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.
文摘Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.
文摘INTRODUCTIONMolecular biology has made a tremendous impact on thediagnosis and treatment of liver diseases.In particular,advances in molecular biology made possible the
基金Supported by The National Institutes of Health,NO.DK080812
文摘Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.
基金This study was supported by the grant of the 1551 French-Thai cooperation PHC SIAM 2011(project 25587RA)and the Mae Fah Luang University funded grant“Taxonomy,Phylogeny and cultivation of Lentinus species in northern Thailand”(MFU/54101020048)this study was financially supported by the project“Value added products from basidiomycetes:Putting Thailand’s biodiversity to use”(BRN049/2553)by the National Research Council of Thailand(NRCT)to study medicinal fungi+1 种基金the National Research Council of Thailand(NRCT),project-Taxonomy,Phylogeny and cultivation of Lentinus species in northern Thailand(NRCT/55201020007)the Thailand Research Fund grant-Taxonomy,Phylogeny and biochemistry of Thai Basidiomycetes(BRG 5580009).The authors would also like to acknowledge University Malaya research grants:CG037-2013 Phylogeny,taxonomy,relationships and biotechnological potential of sooty moulds and RG203-12SUS Isolation and structural elucidation of antimicrobial compounds for saprophytic and endophytic fungi of Peninsular Malaysia through bioassay guided fractionation of secondary metabolites extract.
文摘Exploration of natural sources for novel bioactive compounds has been an emerging field of medicine over the past decades,providing drugs or lead compounds of considerable therapeutic potential.This research has provided exciting evidence on the isolation of microbe-derived metabolites having prospective biological activities.Mushrooms have been valued as traditional sources of natural bioactive compounds for many centuries and have been targeted as promising therapeutic agents.Many novel biologically active compounds have been reported as a result of research on medicinal mushrooms.In this review,we compile the information on bioactive structure-elucidated metabolites from macrofungi discovered over the last decade and highlight their unique chemical diversity and potential benefits to novel drug discovery.The main emphasis is on their anti-Alzheimer,antidiabetic,anti-malarial,anti-microbial,anti-oxidant,antitumor,anti-viral and hypocholesterolemic activities which are important medicinal targets in terms of drug discovery today.Moreover,the reader’s attention is brought to focus on mushroom products and food supplements available in the market with claimed biological activities and potential human health benefits.
基金supported by the National Institutes of Health(Grant No.2R01CA151610)Department of Defense(Grant No.W81XWH-18-1-0067)a Samuel Oschin Cancer Institute Discovery Fund Award and Community Outreach and Engagement Developmental Fund Award.
文摘A novel coronavirus known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread across the world,prompting the World Health Organization to declare the coronavirus disease of 2019(COVID-19)a public health emergency of international concern.Cancer patients are regarded as a highly vulnerable population to SARS-CoV-2 infection and development of more severe COVID-19 symptoms,which is possibly due to the systemic immunosuppressive state caused directly by tumor growth and indirectly by effects of anticancer treatment.Currently,much effort has been directed toward studying the pathogenesis and treatment of COVID-19,but the risk profiles,prognoses,and treatment outcomes in cancer patients remain unclear.Based on the current literature,we summarize the risk profiles,clinical and biochemical characteristics,and therapy outcomes of COVID-19 infections in cancer patients.The challenges in the clinical care of cancer patients with COVID-19 are discussed.The goal of this review is to stimulate research to better understand the biological impact and prognoses of COVID-19 infections in cancer patients,thus facilitating improvement of the clinical management of these patients.
文摘New hepatitis B virus(HBV)infections are decreasing owing to improved antiviral therapy and increased HBV vaccination worldwide;however,the number of HBV infections remains a major cause of liver carcinogenesis.HBV triggers cytotoxic immunity to eliminate HBV-infected cells.Therefore,the HBV pathophysiology changes in persistently infected individuals depending on host immune responses and HBV DNA proliferation state.To prevent liver cirrhosis and carcinogenesis caused by HBV,it is important to treat HBV infection at an early stage.Active treatment is recommended for the immunoactive hepatitis B surface-antigen-positive and-negative phase,but not during the immune-inactive phase or immune-tolerant phase;instead,follow-up is recommended.However,these patients should be monitored through regular blood tests to accurately diagnose the immune-inactive or-tolerant phases.The treatment regimen should be determined based on the age,sex,family history of liver cancer,and liver fibrosis status of patients.Early treatment is often recommended due to various problems during the immune-tolerant phase.This review compares the four major international practice guidelines,including those from the Japanese Society of Hepatology,and discusses strategies for chronic hepatitis B treatment during the immune-tolerant,immune-inactive,and resolved phases.Finally,recommended hepatitis B antiviral therapy and follow-up protocols are discussed.
